In this study, we found that abnormally up-regulated expression of ISL-1 in NHL cells obviously facilitated cell proliferation in vitro and significantly enhanced lymphoma development in vivo, providing the first evidence that ISL-1 could promote non-Hodgkin lymphomagenesis and specific disruption of ISL-1 could be capable of inhibiting NHL cells with high endogenous levels of ISL-1. The gene discussed is ISL1; the disease is non-Hodgkin lymphoma.